Gastroesophageal reflux disease (“GERD”) is a condition in which the lower esophageal sphincter (“LES”) is unable to function properly resulting in the reflux of stomach secretions, in the forms of acid and enzymes, into the esophagus. Exposure of the esophagus epithelium to these secretions, where there is no anatomical or physiological protection, results in deterioration and/or destruction of the lining of the esophagus lumen. GERD is a major health care problem in the United States. 44% of Americans experience monthly heartburn, and it has been estimated that 5–10% of the US population (14–28 million adults) suffer from “significant (daily) heartburn”. There is a wide range in ages of the afflicted, but GERD is more common in individuals over the age of 50. In fact, GERD appears to be second only to psychiatric illness in terms of its effect on overall quality of life. Symptoms of this condition include chronic indigestion or heartburn, inability to eat, discomfort in swallowing, asthma, regurgitation, and chest pain. Prolonged exposure can lead to esophagitis or linear streaking and ulceration of the esophagus epithelium. In the long term, esophagitis can lead to a condition known as Barrett's esophagus, in which there is extreme damage to the lining of the esophagus and which is believed to be a pre-cursor to cancer of the esophagus. Barrett's esophagus has attained national importance as it is associated with an increased risk of adenocarcinoma of the gastroesophageal junction, which has become the most rapidly growing cancer in middle-aged white males. In fact, in a recent article in the New England Journal of Medicine, researchers reported that GERD, even when treated with medication, can lead to an increased risk of esophageal cancer (Lagergren et al., “Symptomatic Gastroesophageal Reflux as a Risk Factor for Esophageal Adenocarcinoma,” New England Journal of Medicine, 340(11):825–31 (1999)). It is clear, therefore, that GERD represents a significant medical concern. Consequently, it has been the target of several therapeutic approaches.
There are several different treatment options for GERD for varying stages of disease progression and discomfort experienced by the patient. The least aggressive approach is modification of lifestyle and diet. Changes are made to daily eating habits and posture along with altering food consumption. These changes are intended to diminish secretion of acid and enzymes in the stomach. This approach does not address the sphincter dysfunction and, in most cases, is used in conjunction with other treatment options. The results from non-surgical options are not statistically appealing. Only a small percentage of the patients undergoing these treatments avoid the need for future surgical treatment once the disease and its symptoms have progressed. Moreover, these methods call for an overall life adjustment and can result in an enormous life-long financial burden for the patient without correcting or repairing the physiological malfunction.
The mainstay of current therapy is still pharmacological suppression of acid production, which is effective in 90% of patients. There are a wide range of new medications for treatment of reflux disease including omeprazole and other proton pump inhibitors. However, because GERD is a chronic disease, treatment with medication must be continuous, and symptoms recur in 80% when treatment with medication is terminated. Further, the most effective drugs (proton pump inhibitors) are also the most expensive, and the cost of treatment with medication is between $1500–2000 per patient per year. Overall, it has been estimated that over $14 billion is spent annually on heartburn medications.
There are several invasive treatment procedures that address the dysfunction of the sphincter to correct reflux disorders. Fundoplication is a surgical procedure where the fundus of the stomach is wrapped around the gastroesophageal junction and sutured to the esophagus. The intra-gastric pressure in the fundus is translated to the sphincter enabling it to resist the reflux of the stomach contents into the esophagus. The most common fundoplication procedure currently used is the Nissen procedure. The Nissen approach involves complete wrapping of the gastroesophageal junction with the fundus. This treatment corrects the malfunction of the sphincter but is an invasive surgery, requiring general anesthesia and hospitalization (even with the increasingly popular laparascopic approach), and may result in side-effects, such as gas-bloat syndrome. In fact, a study evaluating 344 patients over a 10 year period found that the morbidity and mortality rates for this procedure were 17% and 1%, respectively (Urschel, “Complications of Antireflux Surgery,” Am. J. Surg., 166(1):68–70 (1993)).
A less invasive method of performing fundoplication is reported in U.S. Pat. No. 5,088,979 to Filipi et al. This method involves inserting a device containing a plurality of needles into the esophagus. Once extended, the needles are designed to engage the esophagus and allow the operator to fold the wall beyond the gastroesophageal junction. A stapling device, introduced percutaneously through a channel in the stomach, is used to secure the gastroesophageal junction to the surrounding stomach wall. U.S. Pat. No. 5,676,674 to Bolanos et al. describes a modified version of the approach above, whereby the invagination of the esophageal wall as well as fastening are both performed transorally. All of these procedures are still traumatic to the LES and result in risks associated with gastroesophageal leaks, infection, and foreign body reactions.
Most of the commonly performed surgical procedures alleviate the condition of reflux through the correction of the sphincter dysfunction at a cost of creating more potential complications. These procedures are invasive and must be performed by specially trained doctors. Recovery time can last up to several weeks, translating into significant cost and inconvenience for the patient. Even with the prospect of a substantial improvement in quality of life, most patients elect not to have corrective surgical procedures due to their invasive nature.
Other less invasive thermal approaches have been investigated for creating lesions in the LES which provide improved competence for the sphincter. McGouran et al., “A Laser-Induced Scar at the Cardia Increases the Yield Pressure of the Lower Esophageal Sphincter,” Gastrointest. Endosc., 36(5):439–443 (1990) describes the use of a Nd:YAG laser to produce fibrous scar at the cardia in a canine model. However, applying thermal energy in the fashion described is accompanied by significant risks, as evidenced by one subject dying from gastric perforation 10 days after lasing.
Yet another thermal approach is described in U.S. Pat. No. 6,044,846 to Edwards. In this procedure, a device is introduced to the gastroesophageal junction endoscopically where a balloon is then inflated. The procedure further involves inserting RF electrodes into the junction through the epithelium and passing a cold fluid over the balloon to protect the epithelial lumen of the esophagus. The electrodes deliver RF energy which induces thermal coagulation of muscular tissue in the esophagus. This process is then repeated multiple times along the length of the junction over a period of about 40 minutes. The coagulated tissue provides support for the sphincter, allowing it to resist the reflux of the stomach contents into the esophagus. However, this procedure requires insertion of the RF electrodes into the wall of the esophagus and, therefore, is still traumatic to the mucosal layer of the LES. Also, the procedure requires multiple treatments along a length of the LES to effect the desired lesion. Precise positioning during the multiple treatments must be maintained to prevent overlap of thermally treated tissues.
For these and other reasons, a need remains for alternative methods for correction of GERD. The present invention, in part, is directed to meeting this need.